Combined HIV-1 Envelope Systemic and Mucosal Immunization of Lactating Rhesus Monkeys Induces a Robust Immunoglobulin A Isotype B Cell Response in Breast Milk

Abstract

Maternal vaccination to induce anti-HIV immune factors in breast milk is a potential intervention to prevent postnatal HIV-1 mother-to-child transmission (MTCT). We previously demonstrated that immunization of lactating rhesus monkeys with a modified vaccinia More than 200,000 new pediatric human immunodeficiency virus (HIV) infections occur annually via mother-to-child transmission (MTCT), nearly half through breastfeeding (1). Antiretroviral (ARV) drugs can dramatically reduce the rate of MTCT, but in areas of high HIV prevalence, acute HIV infection in pregnant and postpartum women as well as poor access and adherence to ARV treatment throughout the breastfeeding period has limited progress in the prevention of breast milk transmission (2). According to UNAIDS in 2014, only 68% of HIV-infected pregnant women in low-and middle-income countries received ARV therapy during pregnancy, and only 61% of those women continued this therapy postpartum (3). Despite the risk of HIV acquisition, breastfeeding is necessary for infant survival in many regions of the world, as breastfed infants have lower rates of diarrheal and respiratory infections (4). It is well established that antibodies are transferred to infants via the placenta and through breast milk consumption (5); thus, maternal immunization could

Vaccine-Elicited Mucosal and Systemic Antibody Responses Are Associated with Reduced Simian Immunodeficiency Viremia in Infant Rhesus Macaques

“…A subsequent study by the same group showed that strong HIV Env-specific IgA responses could be induced in lactating macaques by vaccination (64). Our results provide evidence that protective mucosal IgA responses can also be induced by vaccination of the infant and thereby have the potential to provide long-term protection against viral acquisition compared to transient protection by maternal antibodies.…”

Impact of Poxvirus Vector Priming, Protein Coadministration, and Vaccine Intervals on HIV gp120 Vaccine-Elicited Antibody Magnitude and Function in Infant Macaques

“…BAMA was performed as described previously (54)(55)(56)(57)(58)(59). Briefly, HIV antigens were conjugated to polystyrene beads (Bio-Rad) and the binding of plasma IgG to the bead-conjugated HIV antigens was measured.…”

Tissue memory B cell repertoire analysis after ALVAC/AIDSVAX B/E gp120 immunization of rhesus macaques

“…genotype for Fcγ receptor IIIa were used as the source of effector cells. CD4 + T cells were activated and infected with AE.CM235 as described (43), and binding to AE.CM235-infected target cells was determined by indirect surface immunofluorescence analysis as described (44).…”